Associate Professor Jodie Simpson

A breath of fresh air

Dr
Jodie Simpson's pioneering research has changed the focus of asthma treatment
and promises new relief for many who suffer from the disease.

Making the
transition from pure science to medical research involved a leap of faith for
Dr Jodie Simpson, but the accomplished asthma researcher has not looked back
since joining the University of Newcastle's leading respiratory group. The
chemistry graduate's science background prompted her to approach research
questions with a different perspective and subsequently led to a breakthrough
finding about asthma subtypes that has brought her international recognition in
the field.

Simpson was
appointed as a research assistant with the respiratory team, based at the
Hunter Medical Research Institute (HMRI), in 1997 after completing her Honours
in chemistry. When she began studying asthma, the accepted treatment paradigm
was using steroid-based medications to target inflammation in the airways
caused by increased levels of eosinophils (a type of white blood cell). However,
Simpson was puzzled by the fact that some asthma sufferers had normal levels of
eosinophils, which led her to question whether there could be more than one
type of the disease.

"I could
never understand why it was assumed that all asthma was due to increased
eosinophils when only about half of the patient studies we saw had that
characterisation," Simpson reflects.

Encouraged
by a small numberof scholarly
reports advocating a similar theory, Simpson embarked in 2002 on an ambitious
PhD project investigating the inflammatory pathways of asthma, counting cells
in sputum samples and analysing levels of enzymes and proteins. Simpson
concluded that there were four subtypes of asthma and, significantly,
identified a non-eosinophilic category common among people who did not respond
well to conventional, steroid-based treatments. This subtype is characterised
by higher levels of a different white blood cell, called the neutrophil.

Simpson's
research led to a randomised control trial, conducted in Newcastle, which produced another breakthrough finding, published in 2008 in the American Journal of Critical and Respiratory
Care Medicine. The study established that treating people who suffered from
non-eosinophilic asthma with macrolide antibiotics successfully reduced their
neutrophil levels and resulted in a clinical improvement in their condition.
"It was a small study, but novel at the time, and it showed that identifying the
inflammatory phenotype was important for the effective management of asthma,"
Simpson explains.

That
original eight-week, 45-person study has since evolved into a four-year, 420-person
national trial led by Professor Peter Gibson, with whom Simpson has worked
closely, and funded by the National Health and Medical Research Council. The
$2.9 million AMAZES trial (Asthma
and Macrolides: the Azithromycin Efficacy and Safety Study) seeks to determine
whether treating asthmatics with macrolides in addition to their normal
medication can reduce the incidence of severe attacks, known as exacerbations,
and ease their general symptoms.

"The focus
of the AMAZES study is treatment but it has all developed from the original
idea of characterising subtypes of asthma," Simpson comments. "Instead of a
blanket treatment for everyone who has asthma, we can now move towards a more
individualised approach, drawing from a range of effective treatments."

As well as
working on the AMAZES trial, Simpson has instigated a series of peripheral
studies aimed at increasing understanding of non-eosinophilic asthma. One
project is testing the extent to which sufferers can reduce their steroid
medication without a detrimental impact on their health; another is testing
alternatives to macrolide antibiotics for reducing inflammation; and a third is
investigating possible triggers for the condition, such as reflux and cough.
She is also working with colleague Dr Katie Baines to advance the
characterisation of asthma subtypes through gene expression.

"Substantial
progress has been made in understanding non-eosinophilic asthma but there is far
more that we need to know," Simpson acknowledges. "We want to attack it from all angles."

Off to a flying start

How does a
chemistry graduate come to supervise a medical trial for her first postdoctoral
project? For Dr Jodie Simpson, the encouragement of her supervisor and mentor
Professor Peter Gibson was critical to her rapid and successful induction to
the field of asthma research. Gibson is co-director of the HMRI Viruses, Infections/Immunity, Vaccines
and Asthma (VIVA) Program and has
been an influential figure in Simpson's career.

"What he
did from the beginning was provide opportunity," Simpson asserts. "I came to
the team with an Honours degree in chemistry and he gave me the chance to learn
about the clinical side of research and participate in it. To be able to lead a
clinical trial for my first project after my PhD was such a wonderful
opportunity."

The insight
into clinical issues that Simpson gained from working with Gibson has greatly
enhanced her work. "When you are in the lab counting cells and measuring
proteins, you can lose the sight of the fact that this is all about a person
out there who is struggling to breathe and function," she advises. "Working in
this team, where we can combine basic science and clinical work, has given me a
more rounded perspective."

The mother
of two toddlers acknowledges that the supportive environment at the University
and HMRI for researchers with young families has been critical to her work. "As
researchers we are passionate about what we do and it is important to have the
support to remain productive during periods where we might have to modify our
working commitments."

Career Summary

Biography

Jodie Simpson is a senior research fellow in The University of Newcastle’s Priority Research Centre for Asthma and Respiratory Disease and the current holder of the Australian Respiratory Council’s Ann Woolcock Research Fellowship.

Her research focuses on the inflammatory biomarkers of airways disease and she has a particular interest in innate immune pathways and their role in airways disease. She has developed several important assays for the assessment of inflammatory mediators in airway secretions and continues to work on assessment of novel markers of airway inflammation.

In 2005, Jodie completed her PhD where she identified and characterised four inflammatory phenotypes in asthma based on the presence of absence of increased sputum eosinophil and neutrophil proportions. This work has led to further investigations of asthma inflammatory phenotypes using gene expression profiling and recently the identification of novel biomarkers for asthma and COPD.

Dr Simpson designed and conducted the first RCT of macrolide antibiotics in severe refractory asthma, this research was pivotal in her success with a large NHMRC project grant awarded in 2008 to investigate macrolide antibiotic therapy in asthma as a multi-centre RCT (The AMAZES study).

In her earlier work, Dr Simpson demonstrated that macrolide antibiotics are an effective anti-inflammatory therapy in non-eosinophilic refractory asthma. She is currently working on the AMAZES study collaborating with centres around Australia and working on 2 sub-studies, the first looking at macrophage phagocytosis and the second investigating airway and systemic inflammation in asthma subtypes.

Jodie has actively presented her work at national and international scientific meetings and has authored over 50 papers in peer reviewed journals. She is an active participant in research service and teaching as representative on TSANZ research subcommittee and the supervisor of 4 research higher degree students.

Research ExpertiseJodie Simpson is a senior research fellow in The University of Newcastle’s Priority Research Centre for Asthma and Respiratory Disease and the current holder of the Australian Respiratory Council’s Ann Woolcock Research Fellowship. Her research focuses on the inflammatory biomarkers of airways disease and she has a particular interest in innate immune pathways and their role in airways disease

Qualifications

PhD (Medicine), University of Newcastle

Bachelor of Science, University of Newcastle

Bachelor of Science (Honours), University of Newcastle

Keywords

COPD

asthma

asthma and COPD

clinical trials

immune response

induced sputum

inflammation

inflammatory mediators

Fields of Research

Code

Description

Percentage

110203

Respiratory Diseases

100

Professional Experience

UON Appointment

Title

Organisation / Department

Associate Professor

University of NewcastleSchool of Biomedical Sciences and PharmacyAustralia

Background: Asthma is a heterogeneous inflammatory disease and eosinophilic, noneosinophilic and neutrophilic forms are recognised. While clinically similar to eosinophilic asthma... [more]

Background: Asthma is a heterogeneous inflammatory disease and eosinophilic, noneosinophilic and neutrophilic forms are recognised. While clinically similar to eosinophilic asthma, patients with non-eosinophilic asthma have different responses to treatment and little is known about the triggers of symptoms and inflammation. Objective: This study sought to characterise asthma control, exacerbation frequency and potential triggers of non-eosinophilic and specifically neutrophilic asthma such as infection, gastroesophageal reflux disease, and rhinosinusitis. Methods: Adults with asthma (n=65; doctor's diagnosis plus demonstrated response to bronchodilator and/or airways hyperresponsiveness to hypertonic saline) were recruited from the Respiratory and Sleep Medicine Ambulatory Care Service at John Hunter Hospital, NSW, Australia. Questionnaires were administered to assess gastroesophageal reflux disease, rhinosinusitis and asthma control. A sputum induction was performed and sputum was processed for assessment of inflammatory cells, infection, and lipid laden macrophages (Oil Red O). Results: Participants with neutrophilic asthma (n=11, 23%) had a higher frequency of primary care doctor visits for asthma exacerbations and a high prevalence (>70%) of chest infections in the previous 12 months. There was also an increased prevalence of rhinosinusitis (64%) and increased symptoms of gastroesophageal reflux disease compared to those with eosinophilic asthma. Conclusions: The clinical pattern of neutrophilic asthma is different from paucigranulocytic and eosinophilic asthma with evidence of abnormal upper airways responses. Specific and targeted treatment of these airway problems may assist in the control and management of neutrophilic asthma.

ABPA is an important complication of chronic asthma resulting from hypersensitivity to the fungus Aspergillus Fumigatus ( AF}. ABPA is characterised by an intense immune response ... [more]

ABPA is an important complication of chronic asthma resulting from hypersensitivity to the fungus Aspergillus Fumigatus ( AF}. ABPA is characterised by an intense immune response with increased use of oral steroids and potentially progressive lung disease. The aim of this study was to determine if treatment of subjects with ABPA with the antifungal agent Itraconazole (Itz) reduced airway and systemic inflammation. Methods: A randomised double blind placebo controlled trial was performed in stable subjects with ABPA (n=29). Subjects with cystic fibrosis ere excluded. The diagnosis of ABPA was based upon; the presence of asthma, IgE sensitisation to Af. a total serum IgE of lOOOIl'/mL or greater and serum IgG to Af or central bronchiectasis on CT scan. Subjects received Itz 400mg per day (n=15) or placebo (n=14) for 16 weeks. All subjects were reviewed monthly with history, spirometry. sputum induction to measure airway inflammation, serum total IgE and IgG to Af and blood eosinophils. Results: Subjects receiving Itz had a greater reduction in sputum eosinophils from baseline (median fall of 94.5%) compared to placebo (45.4%. p<0.01 ). Those on Itz had a fall in sputum total cell count from baseline (43.9%) compared to a rise in those on placebo (rise 10%. p=0.049). Subjects that received Itz also had a reduction in systemic immune activation; there was a fall in serum IgE (3IOIU/mL) compared to placebo (rise ISIU-'mL, p<0.01) and a fall in IgG to Af(15.4IU/mL) compared to placebo (rise 3.7IU-mL, p=0.03). Conclusion: Treatment of subjects with stable ABPA with Itz 400mg daily reduces eosinophilic airway inflammation along with measures of systemic immune activation. These results imply that Itz is a potential adjunctive treatment for ABPA and this should be further investigated with larger studies of lone term clinical efficacv.

Rationale: Epidemics of acute asthma associated with thunderstorms occur intermittently worldwide, though airway inflammation during these acute episodes has not been characterise... [more]

Rationale: Epidemics of acute asthma associated with thunderstorms occur intermittently worldwide, though airway inflammation during these acute episodes has not been characterised. The aim of this study was to characterise airway inflammation in acute thunderstorm asthma. Methods: Cases were recruited after presentation to the emergency room (ER) \vith acute asthma immediately following a thunderstorm (n=6). They were compared to controls that were atopic asthmatics that had presented with acute asthma to the ER prior to the thunderstorm. Subjects had spirometry, sputum induction and allergy skin tests acutely and at review 4 weeks later. Results: Thunderstorm (TS) cases were more likely to have a history of hay fever and less likely to be on inhaled steroids prior to presentation. Both groups had a similar degree of moderate to severe acute airways obstruction (p=l ,0). TS cases had elevated sputum eosinophils (14.8% of total cell count) compared to controls (1%, p < 0.01). TS cases had higher sputum eosinophil cationic protein (ECP) (11686ng/mL) compared to controls (1883, p=0.02) acutely. When adjusted for IS use, TS cases had a risk ratio for elevated sputum eosinophils of 2.3 (1.1-4.5). Conclusion: Airway inflammation in acute thunderstorm asthma is characterised by more sputum eosinophilia and eosinophil degranulation compared to other causes of acute asthma.

News

Associate Professor Jodie Simpson from the University of Newcastle's
Priority Research Centre for Asthma and Respiratory Diseases will visit
China from 18 November to 5 December 2014 on the Australia-China Young
Scientists Exchange Program.